Executive Summary & Business Update [Q2 2025 Overview and Key Highlights](index=1&type=section&id=1.1%20Q2%202025%20Overview%20and%20Key%20Highlights) Structure Therapeutics reported strong Q2 2025 results, advancing aleniglipron and ACCG-2671, backed by $786.5 million cash for operations through 2027 - Topline data from oral small molecule GLP-1 receptor agonist aleniglipron ACCESS and ACCESS II studies are on track for **year-end 2025** readouts[1](index=1&type=chunk)[2](index=2&type=chunk) - Aleniglipron clinical development program expanded to optimize competitive positioning and Phase 3 program design[1](index=1&type=chunk)[2](index=2&type=chunk) - Oral small molecule amylin receptor agonist (ACCG-2671) Phase 1 initiation anticipated by **year-end 2025**[1](index=1&type=chunk)[2](index=2&type=chunk) Cash Position as of June 30, 2025 | Metric | Amount (Millions) | | :------------------------------------ | :---------------- | | Cash, cash equivalents and short-term investments | $786.5 | - The strong financial position is expected to fund projected operations and key clinical milestones through at least **2027**[1](index=1&type=chunk)[13](index=13&type=chunk) Recent and Upcoming Milestones [Aleniglipron (GSBR-1290) Development](index=2&type=section&id=2.1%20Aleniglipron%20(GSBR-1290)%20Development) Structure Therapeutics updated on aleniglipron, with ACCESS/ACCESS II data due year-end 2025 and new studies initiated for competitive positioning [Ongoing ACCESS and ACCESS II Studies](index=2&type=section&id=2.1.1%20Ongoing%20ACCESS%20and%20ACCESS%20II%20Studies) - The fully enrolled ACCESS and ACCESS II studies are on track for topline **36-week** data readouts by **year-end 2025**[3](index=3&type=chunk) - ACCESS study enrolled approximately **220 adults**, evaluating doses up to **120 mg** with a slower four-week titration schedule[6](index=6&type=chunk) - ACCESS II study enrolled approximately **80 adults**, evaluating higher doses (**180 mg** and **240 mg**) with a slower four-week titration schedule[6](index=6&type=chunk) [Expanded Data Collection from ACCESS and ACCESS II Studies](index=2&type=section&id=2.1.2%20Expanded%20Data%20Collection%20from%20ACCESS%20and%20ACCESS%20II%20Studies) - ACCESS Open Label Extension (OLE) allows patients to roll over for longer-term weight loss effects and expanded safety data[4](index=4&type=chunk) - ACCESS II Extension continues patients on assigned doses to **44 weeks**, providing an additional **eight weeks** of double-blinded safety, tolerability, and efficacy data, particularly for higher dose arms (**180 mg** and **240 mg**)[4](index=4&type=chunk) [Additional Aleniglipron Studies](index=2&type=section&id=2.1.3%20Additional%20Aleniglipron%20Studies) - Three new aleniglipron clinical studies are being conducted to generate additional data for competitive positioning and Phase 3 program design[5](index=5&type=chunk) - A Phase 2 study to assess a maintenance switching strategy from an approved injectable GLP-1 receptor agonist to oral aleniglipron is expected to start in **Q3 2025**[7](index=7&type=chunk) - A Phase 2 body composition study to assess the effect of aleniglipron on body fat loss over **40 weeks** is expected to start in **Q3 2025**[7](index=7&type=chunk) - A Phase 2 study in patients with type 2 diabetes mellitus (T2DM) is anticipated to start in **Q4 2025**, with data potentially supporting a T2DM cohort in the Phase 3 obesity program[8](index=8&type=chunk) [Other Pipeline Programs](index=3&type=section&id=2.2%20Other%20Pipeline%20Programs) Structure Therapeutics updated its diverse pipeline, advancing ACCG-2671 to Phase 1 and completing other early-stage studies [Oral Small Molecule Amylin Receptor Agonists (ACCG-2671)](index=3&type=section&id=2.2.1%20Oral%20Small%20Molecule%20Amylin%20Receptor%20Agonists%20(ACCG-2671)) - IND-enabling activities for ACCG-2671 are ongoing, with a first-in-human Phase 1 clinical study planned by **year-end 2025**[12](index=12&type=chunk) - New preclinical data for ACCG-2671 demonstrated high binding affinity, balanced potency, and significant, dose-dependent body weight reductions in diet-induced obese rats[12](index=12&type=chunk) - Combination therapy of ACCG-2671 with semaglutide resulted in superior weight loss compared to monotherapy of either compound[12](index=12&type=chunk) [Oral Small Molecule Metabolic Pipeline and Potential Combinations](index=3&type=section&id=2.2.2%20Oral%20Small%20Molecule%20Metabolic%20Pipeline%20and%20Potential%20Combinations) - Structure Therapeutics is developing GIPR selective agonists and antagonists, and GLP-1R/GIPR combinations to treat obesity and related diseases[12](index=12&type=chunk) - The company is also developing GCGR selective agonists and GLP-1R/GCGR combinations for obesity and related diseases[12](index=12&type=chunk) - ANPA-0073, a Phase 2 ready biased APJR agonist for selective or muscle-sparing weight loss, completed a Phase 1 study with good tolerability. Long-term toxicology studies are underway, expected by **year-end 2025**[12](index=12&type=chunk) [Oral Small Molecule LPA1R Program (LTSE-2578)](index=3&type=section&id=2.2.3%20Oral%20Small%20Molecule%20LPA1R%20Program%20(LTSE-2578)) - Structure Therapeutics successfully finished a Phase 1 single and multiple ascending dose clinical study of LTSE-2578, an oral small molecule antagonist for Idiopathic Pulmonary Fibrosis (IPF)[11](index=11&type=chunk) - The study showed no evidence of dose-dependent LTSE-2578-related adverse events, including clinical, laboratory, and electrocardiogram recordings, and no SAEs were observed[11](index=11&type=chunk) Financial Performance [Q2 2025 Financial Highlights](index=4&type=section&id=3.1%20Q2%202025%20Financial%20Highlights) Structure Therapeutics reported a strong $786.5 million cash position, but increased expenses led to a higher Q2 2025 net loss Cash Position | Metric | June 30, 2025 | | :------------------------------------ | :------------ | | Cash, cash equivalents and short-term investments | $786.5 million | - Current cash, cash equivalents and short-term investments are expected to fund projected operations and key clinical milestones through at least **2027**[13](index=13&type=chunk) Research and Development (R&D) Expenses (YoY Change) | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (YoY) | | :------------------- | :----------------- | :----------------- | :----------- | | R&D Expenses | $54.7 | $22.1 | +$32.6 million | - The increase in R&D expenses was primarily due to increases related to pre-clinical research and development, clinical trial costs, and personnel-related expenses to support the GLP-1R franchise[14](index=14&type=chunk) General and Administrative (G&A) Expenses (YoY Change) | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (YoY) | | :------------------- | :----------------- | :----------------- | :----------- | | G&A Expenses | $15.7 | $11.3 | +$4.4 million | - The increase in G&A expenses was primarily due to increases in employee expenses as infrastructure expanded to support growth as a publicly-traded company[15](index=15&type=chunk) Net Loss (YoY Change) | Metric | Q2 2025 (Millions) | Q2 2024 (Millions) | Change (YoY) | | :------- | :----------------- | :----------------- | :----------- | | Net Loss | $61.7 | $26.0 | +$35.7 million | - Non-cash share-based compensation expense increased to **$7.5 million** in Q2 2025 from **$4.2 million** in Q2 2024[16](index=16&type=chunk) [Condensed Consolidated Statements of Operations](index=6&type=section&id=3.2%20Condensed%20Consolidated%20Statements%20of%20Operations) The condensed consolidated statements of operations show a significant increase in operating expenses, particularly in research and development, leading to a higher net loss for both the three and six months ended June 30, 2025, compared to the prior year periods Condensed Consolidated Statements of Operations (Unaudited, In thousands) | | THREE MONTHS ENDED | | | | SIX MONTHS ENDED | | | | | :-------------------------- | :--- | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | | JUNE 30, | | | JUNE 30, | | | | | | 2025 | | 2024 | 2025 | | 2024 | | Operating expenses: | | | | | | | | | | Research and development | $ 54,710 | | $ 22,050 | $ 97,577 | | $ 42,729 | | General and administrative | 15,741 | | 11,266 | 29,185 | | 22,602 | | Total operating expenses | 70,451 | | 33,316 | 126,762 | | 65,331 | | Loss from operations | (70,451) | | (33,316) | (126,762) | | (65,331) | | Interest and other income, net | 8,929 | | 7,335 | 18,505 | | 13,343 | | Loss before provision for income taxes | (61,522) | | (25,981) | (108,257) | | (51,988) | | Provision for income taxes | 139 | | 53 | 237 | | 82 | | Net loss | $ (61,661) | | $ (26,034) | $ (108,494) | | $ (52,070) | [Condensed Consolidated Balance Sheet Data](index=6&type=section&id=3.3%20Condensed%20Consolidated%20Balance%20Sheet%20Data) Total assets decreased from $903.3 million to $816.4 million due to reduced cash, with liabilities increasing and equity decreasing Condensed Consolidated Balance Sheet Data (Unaudited, In thousands) | | JUNE 30, | | DECEMBER 31, | | :---------------------------------- | :--- | :--- | :--- | :--- | | | 2025 | | 2024 | | Assets | | | | | | Current assets: | | | | | | Cash, cash equivalents and short-term investments | $ 786,496 | | $ 883,518 | | Prepaid expenses and other current assets | 12,802 | | 7,693 | | Total current assets | 799,298 | | 891,211 | | Property and equipment, net | 3,459 | | 3,478 | | Operating right-of-use assets | 7,484 | | 3,535 | | Other non-current assets | 6,202 | | 5,106 | | Total assets | $ 816,443 | | $ 903,330 | | Liabilities and shareholders' equity | | | | | | Current liabilities: | | | | | | Accounts payable | $ 8,990 | | $ 8,024 | | Accrued expenses and other current liabilities | 27,379 | | 26,299 | | Operating lease liabilities, current portion | 2,664 | | 1,698 | | Total current liabilities | 39,033 | | 36,021 | | Operating lease liabilities, net of current portion | 5,012 | | 2,164 | | Other non-current liabilities | 317 | | 302 | | Total liabilities | 44,362 | | 38,487 | | Total shareholders' equity | 772,081 | | 864,843 | | Total liabilities and shareholders' equity | $ 816,443 | | $ 903,330 | About Structure Therapeutics [Company Overview](index=4&type=section&id=4.1%20Company%20Overview) Structure Therapeutics is a clinical-stage biopharmaceutical company developing oral small molecule treatments for chronic metabolic and cardiopulmonary conditions - Structure Therapeutics is a science-driven clinical-stage biopharmaceutical company[17](index=17&type=chunk) - Focuses on discovering and developing innovative oral small molecule treatments for chronic metabolic and cardiopulmonary conditions with significant unmet medical needs[17](index=17&type=chunk) - Utilizes a next-generation structure-based drug discovery platform to establish a robust GPCR-targeted pipeline[17](index=17&type=chunk) - Aims to surpass scalability limitations of traditional biologic and peptide therapies and make treatments accessible to more patients globally[17](index=17&type=chunk) Forward-Looking Statements [Disclaimer and Risk Factors](index=5&type=section&id=5.1%20Disclaimer%20and%20Risk%20Factors) This section cautions that forward-looking statements are subject to risks and uncertainties, with no obligation to update - The press release contains "forward-looking statements" as defined by the Private Securities Litigation Reform Act of 1995[18](index=18&type=chunk) - Statements concern future plans, prospects, expected timing of data readouts, study initiations, cash runway, and potential benefits/efficacy of therapeutic candidates[18](index=18&type=chunk) - Readers are cautioned that actual results, levels of activity, safety, performance, or events could differ materially due to various risks and uncertainties, including those described in SEC filings[18](index=18&type=chunk) - The Company undertakes no obligation to update such statements to reflect events or circumstances that exist after the date on which they were made, except as required by law[18](index=18&type=chunk) Contact Information [Investor and Media Relations](index=6&type=section&id=6.1%20Investor%20and%20Media%20Relations) This section provides contact details for investor and media inquiries related to Structure Therapeutics - Investors can contact Danielle Keatley at ir@structuretx.com[23](index=23&type=chunk) - Media inquiries can be directed to Dan Budwick of 1AB at Dan@1abmedia.com[23](index=23&type=chunk)

Core Insights - Structure Therapeutics is advancing its clinical development programs for aleniglipron, an oral small molecule GLP-1 receptor agonist, with topline data readouts expected by the end of 2025 [1][2] - The company is also initiating a Phase 1 study for ACCG-2671, an oral small molecule amylin receptor agonist, anticipated by year-end 2025 [1][2] - As of June 30, 2025, the company reported a strong financial position with cash, cash equivalents, and short-term investments totaling $786.5 million, expected to fund operations through at least 2027 [1][9] Clinical Development - The ACCESS and ACCESS II studies for aleniglipron are fully enrolled, with approximately 220 and 80 adults participating, respectively, and are designed to evaluate various doses and long-term effects [3][4] - Additional studies for aleniglipron include an open-label extension and an extension of ACCESS II to gather more long-term data on safety and efficacy [4][5] - The company is also developing a pipeline of oral small molecule therapeutics targeting obesity and related metabolic diseases, focusing on combinability and long-term weight loss maintenance [2][10] Financial Performance - Research and Development (R&D) expenses for Q2 2025 were $54.7 million, a significant increase from $22.1 million in Q2 2024, driven by clinical trial costs and pre-clinical research [10][11] - General and Administrative (G&A) expenses rose to $15.7 million in Q2 2025 from $11.3 million in Q2 2024, reflecting increased personnel-related expenses [11] - The net loss for Q2 2025 was $61.7 million, compared to a net loss of $26.0 million in Q2 2024, with non-cash share-based compensation contributing to the loss [12][16] Pipeline and Future Studies - Structure Therapeutics is planning to initiate several new studies, including a Phase 2 body composition study and a Phase 2 study in patients with type 2 diabetes mellitus (T2DM), both expected to start in late 2025 [10][12] - The company is also advancing its oral small molecule programs targeting various receptors, including GIPR and GCGR, to treat obesity and related diseases [10][12] - ACCG-2671 has shown promising preclinical results, demonstrating significant body weight reductions in diet-induced obese rats and potential for combination therapy with semaglutide [10][12]

Summary of Structure Therapeutics (GPCR) FY Conference Call Company Overview - Structure Therapeutics focuses on accessibility in the obesity treatment space, addressing healthcare inequality [3][4] - The company specializes in oral small molecules, particularly in converting biologic peptide drugs into oral forms [4] Key Products and Pipeline - **Aleniglipperon**: The most advanced oral small molecule GLP-1, currently in two Phase 2b studies (ACCESS and ACCESS 2) [4][5] - The company has a broad small molecule portfolio, including amylin, GIP, GCG, and apelin small molecules [5] - Emphasis on fixed-dose combinations to provide patients with more treatment options [5][14] Market Insights - The obesity market is evolving, with increasing recognition of obesity as a disease and a pandemic [8] - There is a growing demand for both oral and injectable treatments, with many patients preferring oral options for convenience [6][7] - The obesity epidemic is linked to various chronic conditions, expanding the market opportunities [8] Clinical Development - **Phase 2b Studies**: - ACCESS study: 36-week study with 220 participants, testing a maximum dose of 120 mg [31] - ACCESS 2 study: Higher doses of 180 mg and 240 mg, focusing on tolerability and efficacy directionality [34][36] - The company aims to demonstrate equivalence in efficacy and tolerability compared to competitors like orfagliptin [40][41] Regulatory Environment - Recent FDA guidance acknowledges chronic weight management as a pandemic, with no cardiovascular outcome studies required for obesity treatments [49][50] - The FDA emphasized the importance of maintenance therapy to prevent weight regain [51] Strategic Partnerships - Structure Therapeutics is exploring strategic partnerships for commercialization to enhance accessibility of their drugs [56][58] - The company is open to partnerships for various indications beyond chronic weight management, including type 2 diabetes and chronic kidney disease [54][56] Financial Position - As of Q1, the company reported a cash runway of $837 million, sufficient to fund operations until the end of 2027 [97][98] Future Directions - The company is focused on executing its clinical trials and exploring additional small molecule candidates, including GIP and GCG [88][93] - There is a strong emphasis on the potential of amylin small molecules and their role in combination therapies for obesity treatment [86][90] Conclusion - Structure Therapeutics is positioned to capitalize on the growing obesity treatment market with its innovative oral small molecules and strategic focus on accessibility and partnerships [56][66]

PART I. FINANCIAL INFORMATION For the three months ended March 31, 2025, the company reported a net loss of $46.8 million, an increase from a $26.0 million net loss in the same period of 2024, driven by higher research and development expenses. The balance sheet shows total assets of $866.5 million and total shareholders' equity of $824.6 million as of March 31, 2025. The company used $52.2 million in cash for operating activities during the quarter [Financial Statements (Unaudited)](index=9&type=section&id=Item%201.%20Financial%20Statements%20%28Unaudited%29) For the three months ended March 31, 2025, the company reported a net loss of $46.8 million, an increase from a $26.0 million net loss in the same period of 2024, driven by higher research and development expenses. The balance sheet shows total assets of $866.5 million and total shareholders' equity of $824.6 million as of March 31, 2025. The company used $52.2 million in cash for operating activities during the quarter [Condensed Consolidated Balance Sheets](index=9&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) As of March 31, 2025, the company had total assets of $866.5 million, a decrease from $903.3 million at the end of 2024. This was primarily composed of $152.1 million in cash and cash equivalents and $684.8 million in short-term investments. Total liabilities increased slightly to $41.9 million, while total shareholders' equity decreased to $824.6 million from $864.8 million Condensed Consolidated Balance Sheet Highlights (in thousands) | Account | March 31, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $152,123 | $169,510 | | Short-term investments | $684,759 | $714,008 | | **Total Assets** | **$866,549** | **$903,330** | | Total current liabilities | $36,487 | $36,021 | | **Total Liabilities** | **$41,911** | **$38,487** | | **Total Shareholders' Equity** | **$824,638** | **$864,843** | [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) For the first quarter of 2025, the company reported a net loss of $46.8 million, or ($0.27) per share, compared to a net loss of $26.0 million, or ($0.19) per share, for the same period in 2024. The increased loss was primarily driven by a significant rise in research and development expenses, which grew to $42.9 million from $20.7 million year-over-year Q1 2025 vs Q1 2024 Statement of Operations (in thousands, except per share data) | Metric | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Research and development | $42,867 | $20,679 | | General and administrative | $13,444 | $11,336 | | **Total operating expenses** | **$56,311** | **$32,015** | | Loss from operations | ($56,311) | ($32,015) | | Interest and other income, net | $9,576 | $6,008 | | **Net loss** | **($46,833)** | **($26,036)** | | Net loss per share, basic and diluted | ($0.27) | ($0.19) | [Condensed Consolidated Statements of Shareholders' Equity](index=11&type=section&id=Condensed%20Consolidated%20Statements%20of%20Shareholders%27%20Equity) Total shareholders' equity decreased from $864.8 million at December 31, 2024, to $824.6 million at March 31, 2025. The decrease was primarily due to the net loss of $46.8 million for the quarter, partially offset by $5.9 million in share-based compensation expense and $1.0 million from the exercise of share options - Shareholders' equity decreased by **$40.2 million** during Q1 2025, mainly driven by a net loss of **$46.8 million**[20](index=20&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=12&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) For the three months ended March 31, 2025, net cash used in operating activities was $52.2 million, an increase from $34.1 million in the prior-year period, reflecting higher operating expenses. Net cash provided by investing activities was $34.0 million, primarily from net maturities of short-term investments. Net cash provided by financing activities was $0.8 million from the exercise of share options. Cash and cash equivalents decreased by $17.4 million to end the period at $152.1 million Q1 2025 vs Q1 2024 Cash Flow Summary (in thousands) | Activity | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(52,229) | $(34,080) | | Net cash provided by investing activities | $34,033 | $1,418 | | Net cash provided by financing activities | $809 | $702 | | **Net change in cash and cash equivalents** | **($17,387)** | **($31,960)** | [Notes to Unaudited Condensed Consolidated Financial Statements](index=13&type=section&id=Notes%20to%20Unaudited%20Condensed%20Consolidated%20Financial%20Statements) The notes detail the company's financial position and operations. Key points include the company's belief that its $836.9 million in cash, cash equivalents, and short-term investments are sufficient to fund operations for at least the next 12 months. The company operates as a single segment focused on R&D for chronic diseases. It has significant operating lease commitments totaling $8.6 million and collaboration agreements with Schrödinger that include potential future milestone and royalty payments - The company believes its cash, cash equivalents, and short-term investments of **$836.9 million** as of March 31, 2025, are sufficient to fund operations for **at least the next 12 months**[30](index=30&type=chunk) - The company operates as **one reportable segment**: the research and development of medicines for chronic diseases with unmet medical needs[34](index=34&type=chunk) - The company has collaboration agreements with Schrödinger involving potential future payments, including up to **$17.0 million** in milestones for the Lhotse agreement and up to **$89.0 million** for the Aconcagua agreement, plus **low single-digit royalties**[74](index=74&type=chunk)[78](index=78&type=chunk) [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=29&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's financial performance, highlighting a 107% increase in R&D expenses to $42.9 million in Q1 2025, driven by advancing its clinical programs, particularly aleniglipron. The company's cash, cash equivalents, and short-term investments totaled $836.9 million as of March 31, 2025, which is expected to fund operations and key clinical milestones through at least 2027, excluding Phase 3 registrational studies. The company continues to advance its pipeline, including initiating Phase 2b studies for aleniglipron and a Phase 1 study for LTSE-2578 [Overview](index=29&type=section&id=Overview) Structure Therapeutics is a clinical-stage biopharmaceutical company focused on oral small molecule therapies for chronic diseases, using a structure-based drug discovery platform targeting GPCRs. Its lead candidate, aleniglipron, is in Phase 2b studies for obesity. The pipeline also includes ACCG-2671 (amylin agonist), ANPA-0073 (APJ agonist), and LTSE-2578 (LPA1R antagonist). The company has incurred significant losses since inception and expects them to continue as it advances its pipeline - The company's most advanced candidate, **aleniglipron** (GLP-1R agonist), is in two Phase 2b studies (ACCESS and ACCESS II) for obesity, with topline data expected in **Q4 2025**[83](index=83&type=chunk)[87](index=87&type=chunk) - Other key pipeline programs include ACCG-2671 (amylin agonist) for which a Phase 1 study is expected to start in **Q4 2025**, and LTSE-2578 (LPA1R antagonist) for IPF, which entered a Phase 1 study in June 2024 with initial data expected in **2025**[88](index=88&type=chunk)[89](index=89&type=chunk) - The company outsources all clinical drug manufacturing and has established a manufacturing plan in the U.S. to diversify its supply chain **beyond China**[91](index=91&type=chunk) [Results of Operations](index=37&type=section&id=Results%20of%20Operations) For Q1 2025, R&D expenses increased by 107% to $42.9 million from $20.7 million in Q1 2024, mainly due to higher pre-clinical and clinical trial costs, particularly for aleniglipron. General and administrative expenses rose 19% to $13.4 million due to increased employee expenses to support growth as a public company. Interest income increased to $9.6 million from $6.0 million due to higher cash and investment balances - **R&D expenses increased by $22.2 million (107%)** in Q1 2025 compared to Q1 2024, driven by increased pre-clinical research, clinical trial costs, and personnel expenses[108](index=108&type=chunk) Research and Development Expenses by Program (in thousands) | Product candidate | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Aleniglipron (GSBR‑1290) | $24,985 | $9,535 | | ACCG-2671 | $5,610 | $1,983 | | LTSE‑2578 | $1,426 | $2,162 | | ANPA‑0073 | $1,106 | $1,114 | | Other | $9,740 | $5,885 | | **Total R&D expenses** | **$42,867** | **$20,679** | - **G&A expenses increased by $2.1 million (19%)** in Q1 2025 compared to Q1 2024, primarily from higher employee expenses related to company growth, partially offset by lower consulting fees[111](index=111&type=chunk) [Liquidity and Capital Resources](index=38&type=section&id=Liquidity%20and%20Capital%20Resources) As of March 31, 2025, the company had $836.9 million in cash, cash equivalents, and short-term investments. This position was bolstered by a Follow-On Offering in June 2024 that raised $512.7 million in net proceeds. Management believes current capital is sufficient to fund operations and key clinical milestones through at least 2027, but this excludes the costs of Phase 3 registrational studies for aleniglipron, for which substantial additional capital will be required - As of March 31, 2025, the company had **$836.9 million** in cash, cash equivalents, and short-term investments and an accumulated deficit of **$375.9 million**[113](index=113&type=chunk)[114](index=114&type=chunk) - The company estimates its existing cash will be sufficient to fund operations and key clinical milestones through **at least 2027**, but this **excludes funding for Phase 3 registrational studies of aleniglipron**[94](index=94&type=chunk)[144](index=144&type=chunk) - The company will need **substantial additional capital** to fund future operations, particularly for Phase 3 clinical studies of aleniglipron, and may seek it through equity or debt financings, or collaborations[95](index=95&type=chunk)[117](index=117&type=chunk) [Cash Flows](index=41&type=section&id=Summary%20Statements%20of%20Cash%20Flows) In Q1 2025, net cash used in operating activities was $52.2 million, driven by a net loss of $46.8 million and changes in operating assets. Net cash provided by investing activities was $34.0 million from net maturities of short-term investments. Net cash provided by financing activities was $0.8 million, mainly from the exercise of share options Summary of Cash Flows (in thousands) | Activity | Q1 2025 | Q1 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(52,229) | $(34,080) | | Net cash provided by investing activities | $34,033 | $1,418 | | Net cash provided by financing activities | $809 | $702 | [Quantitative and Qualitative Disclosures About Market Risk](index=45&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) The company states that there were no material changes to its quantitative and qualitative disclosures about market risk during the three months ended March 31, 2025, as compared to those described in its Annual Report on Form 10-K - There were **no material changes** to the company's quantitative and qualitative disclosures about market risk during the first quarter of 2025[132](index=132&type=chunk) [Controls and Procedures](index=45&type=section&id=Item%204.%20Controls%20and%20Procedures) Management, including the CEO and CFO, evaluated the company's disclosure controls and procedures and concluded they were effective as of March 31, 2025. There were no changes in internal control over financial reporting during the quarter that materially affected, or are reasonably likely to materially affect, these controls - Management concluded that as of March 31, 2025, the company's disclosure controls and procedures were **effective at a reasonable assurance level**[134](index=134&type=chunk) - **No changes** in internal control over financial reporting were identified during the quarter ended March 31, 2025, that have materially affected or are likely to materially affect internal controls[135](index=135&type=chunk) PART II. OTHER INFORMATION [Legal Proceedings](index=46&type=section&id=Item%201.%20Legal%20Proceedings) The company reports that it is not currently subject to any material legal proceedings. It acknowledges that it may be involved in ordinary course legal matters in the future - The company is **not currently the subject of any material** governmental investigation, private lawsuit, or other legal proceeding[138](index=138&type=chunk) [Risk Factors](index=46&type=section&id=Item%201A.%20Risk%20Factors) This section details numerous risks that could materially harm the company's business. Key risks include its limited operating history and history of losses, the need for substantial additional capital, the unproven nature of its drug discovery platform, and reliance on third parties for manufacturing and clinical trials. It also highlights risks related to competition, regulatory approval, intellectual property protection, and operating in China. Specific concerns mentioned include the BIOSECURE Act's potential impact on its supplier WuXi AppTec and the inherent uncertainties of clinical development [Risks Related to Our Limited Operating History, Financial Position and Capital Requirements](index=46&type=section&id=Risks%20Related%20to%20Our%20Limited%20Operating%20History%2C%20Financial%20Position%20and%20Capital%20Requirements) The company has a limited operating history, has incurred significant losses since inception ($375.9 million accumulated deficit as of March 31, 2025), and expects losses to continue. It will require substantial additional capital to finance operations, especially for Phase 3 studies, which may not be available on acceptable terms. Failure to obtain capital could force delays or termination of development programs - The company has a **limited operating history**, has incurred **significant operating losses** since inception, and expects to incur significant losses for the **foreseeable future**[140](index=140&type=chunk) - **Substantial additional capital is required** to finance operations, and failure to obtain it may force **delays, limitations, or termination** of product development programs[143](index=143&type=chunk) - Existing cash is estimated to be **sufficient through at least 2027**, but this **excludes Phase 3 registrational studies for aleniglipron**[144](index=144&type=chunk) [Risks Related to the Discovery, Development and Regulatory Approval of Product Candidates](index=50&type=section&id=Risks%20Related%20to%20the%20Discovery%2C%20Development%20and%20Regulatory%20Approval%20of%20Product%20Candidates) The company's drug discovery platform is unproven, and its product candidates are in early clinical development. Drug development is a lengthy, expensive, and uncertain process. Positive early-stage results are not predictive of future success. The company faces risks of clinical trial delays, such as the data collection omission experienced for aleniglipron, and potential rejection of foreign clinical data by the FDA. There is also a risk of serious adverse events emerging in later-stage trials - The company's drug discovery platform is **unproven**, and it is **uncertain** if it can develop any products of commercial value[150](index=150&type=chunk) - The company has **experienced clinical trial delays**, citing a **data collection omission** at a clinical site for its Phase 2a study of aleniglipron, which delayed data reporting[163](index=163&type=chunk) - The company **conducts initial clinical studies outside the U.S.** (e.g., in Australia), and there is a risk that the **FDA or other authorities may not accept data** from these studies, which would delay development[189](index=189&type=chunk) [Risks Related to Our Reliance on Third Parties](index=73&type=section&id=Risks%20Related%20to%20Our%20Reliance%20on%20Third%20Parties) The company relies on third parties for manufacturing, preclinical studies, and clinical trials, which increases risks related to supply, cost, and quality. A key supplier, WuXi STA, is a subsidiary of WuXi AppTec, which has been named in the proposed BIOSECURE Act, potentially disrupting the supply chain. The company also depends on CROs for trial execution and has experienced delays due to their actions - The company **relies on third-party manufacturers**, including **WuXi STA**, a subsidiary of WuXi AppTec. Proposed legislation like the **BIOSECURE Act** could restrict the ability to work with such entities, potentially **disrupting the supply of materials**[205](index=205&type=chunk) - The company **relies on CROs** to conduct clinical studies and has **experienced delays** due to their actions, such as a **data collection omission** at a clinical site during the Phase 2a trial of aleniglipron[213](index=213&type=chunk)[215](index=215&type=chunk) - The company's **collaborations with Schrödinger are critical** for its discovery capabilities. Termination of or failure by Schrödinger to perform under these agreements could **materially harm** the development of product candidates[227](index=227&type=chunk)[228](index=228&type=chunk) [Risks Related to Commercialization of Our Product Candidates](index=85&type=section&id=Risks%20Related%20to%20Commercialization%20of%20Our%20Product%20Candidates) Even if approved, the company's products face significant commercialization hurdles. These include ongoing regulatory obligations, potential failure to achieve market acceptance, and challenges in securing coverage and adequate reimbursement from payors. The company faces substantial competition from large pharmaceutical companies like Eli Lilly and Novo Nordisk in the obesity market. As a company with no commercialization experience, it would need to build a sales and marketing organization or rely on partners - The company faces **substantial competition** from major pharmaceutical and biotechnology companies, including **Eli Lilly, Novo Nordisk, AstraZeneca, and Roche**, who are developing or marketing products for the same indications[253](index=253&type=chunk)[254](index=254&type=chunk) - The company has **no marketing and sales organization or experience** in commercializing products and would need to **invest significant resources** to build these capabilities or rely on third parties[259](index=259&type=chunk) - Market acceptance and sales will depend on **securing coverage and adequate reimbursement** from third-party payors, which is **uncertain** in the current cost-containment environment[249](index=249&type=chunk) [Risks Related to Our Business Operations and Industry](index=95&type=section&id=Risks%20Related%20to%20Our%20Business%20Operations%20and%20Industry) The company's success is highly dependent on its senior management team and its ability to attract and retain qualified personnel. It faces risks related to managing growth, potential loss of R&D tax credits from its Australian subsidiaries, and compliance with complex healthcare fraud and abuse laws. The business is also subject to risks from cybersecurity threats, potential product liability lawsuits, and the impact of healthcare reform like the Inflation Reduction Act (IRA) - The company is **highly dependent on its senior management team** and faces **intense competition** for qualified personnel[265](index=265&type=chunk)[266](index=266&type=chunk) - The company's **Australian subsidiaries may not be able to receive the R&D tax credit**, or could be required to **refund credits** previously received, which would harm business results[271](index=271&type=chunk)[272](index=272&type=chunk) - **Healthcare legislative reforms**, such as the **Inflation Reduction Act (IRA)** which includes Medicare drug price negotiation and inflation rebates, could **negatively impact** the business and ability to sell products profitably[281](index=281&type=chunk)[283](index=283&type=chunk) [Risks Related to Doing Business in China and Our International Operations](index=115&type=section&id=Risks%20Related%20to%20Doing%20Business%20in%20China%20and%20Our%20International%20Operations) The company's operations in China expose it to risks from changes in Chinese political, economic, and legal policies, as well as U.S.-China relations. It must comply with complex and evolving Chinese laws on data security (e.g., Cybersecurity Law, PIPL) and human genetic resources (HGR Regulation). Future securities offerings may require filing with the CSRC under new regulations. The company also faces risks related to currency exchange controls and potential classification as a China resident enterprise for tax purposes - Changes in political and economic policies between China and the United States may **adversely affect** the company's business, financial condition, and results of operations[318](index=318&type=chunk) - The company is subject to **complex Chinese data security laws** (e.g., Cybersecurity Law, Data Security Law, PIPL) and regulations on human genetic resources, which may entail significant compliance expenses and risks[321](index=321&type=chunk)[327](index=327&type=chunk) - Under new CSRC regulations effective March 31, 2023, the company may be required to complete filings with the **CSRC** for future securities offerings, and failure to do so could result in penalties[331](index=331&type=chunk)[332](index=332&type=chunk) [Risks Related to Our Intellectual Property](index=132&type=section&id=Risks%20Related%20to%20Our%20Intellectual%20Property) The company's success depends on its ability to obtain and maintain intellectual property protection for its platform and product candidates. There is a risk that patents may not be issued, or if issued, may not be broad enough or may be invalidated. The company also relies on trade secrets, which are difficult to protect. It faces the risk of third-party infringement claims, which could be costly and time-consuming to defend, and changes in patent law could diminish the value of its IP - The company's ability to successfully commercialize its products is dependent on **obtaining and maintaining sufficient intellectual property protection**, which is **uncertain**[353](index=353&type=chunk) - The company may become involved in **lawsuits alleging infringement** of third-party intellectual property rights, which could be **expensive and have a negative impact** on the business[383](index=383&type=chunk) - **Changes in U.S. patent law**, such as the Leahy-Smith Act, or the patent laws of other countries could **diminish the value of patents** and impair the ability to protect product candidates[397](index=397&type=chunk) [Risks Related to Our ADSs](index=153&type=section&id=Risks%20Related%20to%20Our%20ADSs) The trading price of the company's ADSs is likely to be volatile. Although its auditor is currently subject to PCAOB inspection, future changes could subject it to the HFCA Act, potentially leading to delisting. The company has previously identified and remediated a material weakness in internal controls. Principal shareholders hold significant voting power, and future sales of ADSs could depress the market price. ADS holders have fewer rights than direct shareholders and waive the right to a jury trial for claims arising under the deposit agreement - The trading price of the company's ADSs may be **highly volatile** due to factors such as clinical trial results, regulatory decisions, and market conditions[413](index=413&type=chunk) - While the company's auditor is **currently subject to PCAOB inspection**, if this changes, the company could be subject to the **HFCA Act**, which could lead to **delisting** from Nasdaq[416](index=416&type=chunk)[419](index=419&type=chunk) - The company **previously identified and has since remediated a material weakness** in its internal control over financial reporting as of June 30, 2024[422](index=422&type=chunk)[424](index=424&type=chunk)[425](index=425&type=chunk) [General Risk Factors](index=168&type=section&id=General%20Risk%20Factors) The company faces general risks including the significant costs and compliance burdens of being a public company, particularly after losing its 'emerging growth company' status. Failure to maintain effective internal controls could harm financial reporting reliability. The company is also exposed to risks from natural disasters like earthquakes and fires at its California headquarters, and potential liabilities from the use of hazardous materials in its R&D operations - As a public company, the company must **maintain effective internal controls** over financial reporting, a process that is **costly and challenging**. Failure to do so could **harm investor confidence** and the stock price[452](index=452&type=chunk)[454](index=454&type=chunk) - The company's **headquarters and main research facility are located in an area prone to earthquakes and fires**, and it **lacks a comprehensive disaster recovery plan and earthquake insurance**[463](index=463&type=chunk) - **Failure to comply with Nasdaq's continued listing requirements** could result in the **delisting** of the company's ADSs[467](index=467&type=chunk) [Unregistered Sales of Equity Securities and Use of Proceeds](index=171&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reported no unregistered sales of equity securities during the three months ended March 31, 2025 - There were **no unregistered sales of equity securities** during the three months ended March 31, 2025[468](index=468&type=chunk) [Defaults Upon Senior Securities](index=171&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) The company reported no defaults upon senior securities - **None**[468](index=468&type=chunk) [Mine Safety Disclosures](index=171&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company - **None**[468](index=468&type=chunk) [Other Information](index=171&type=section&id=Item%205.%20Other%20Information) The company reported no other information required to be disclosed under this item - **None**[468](index=468&type=chunk) [Exhibits](index=172&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the Form 10-Q, including the Amended and Restated Memorandum and Articles of Association, forms of deposit agreement and ADR, CEO and CFO certifications (Sections 302 and 906), and XBRL data files - The report includes **standard exhibits** such as organizational documents, **CEO/CFO certifications** under Sarbanes-Oxley Sections 302 and 906, and **Inline XBRL filings**[470](index=470&type=chunk) [Signatures](index=173&type=section&id=Signatures) The report is duly signed by the company's Chief Executive Officer (Raymond Stevens, Ph.D.) and Chief Financial Officer (Jun Yoon) on May 8, 2025 - The report was signed on **May 8, 2025**, by **Raymond Stevens, Ph.D., Chief Executive Officer**, and **Jun Yoon, Chief Financial Officer**[473](index=473&type=chunk)

Exhibit 99.1 Structure Therapeutics Reports First Quarter 2025 Financial Results and Recent Highlights Topline data from oral small molecule aleniglipron (GSBR-1290) Phase 2b ACCESS and ACCESS II studies anticipated by year-end 2025 Oral small molecule amylin receptor agonist (ACCG-2671) Phase 1 initiation anticipated by year-end 2025; New preclinical data to be presented at American Diabetes Association (ADA) 85 Scientific Sessions in June 2025 Strong financial position with cash, cash equivalents and shor ...

Core Insights - Structure Therapeutics is advancing its oral small molecule therapeutics for metabolic diseases, particularly obesity, with significant clinical milestones expected by the end of 2025 [1][2][5] Clinical Development - The Phase 2b ACCESS and ACCESS II studies for aleniglipron (GSBR-1290), an oral small molecule GLP-1 receptor agonist, are fully enrolled and on track for topline data readout by year-end 2025 [5] - ACCESS study enrolled approximately 220 adults with obesity or overweight with weight-related comorbidities, evaluating doses up to 120 mg of aleniglipron [5] - ACCESS II study enrolled approximately 80 adults, evaluating higher doses of aleniglipron (180 mg and 240 mg) [5] - The Phase 1 study for ACCG-2671, an oral small molecule amylin receptor agonist, is anticipated to initiate by year-end 2025 [1][2][5] Financial Position - As of March 31, 2025, the company reported cash, cash equivalents, and short-term investments totaling $836.9 million, expected to fund operations through at least 2027 [7] - Research and Development (R&D) expenses for Q1 2025 were $42.9 million, up from $20.7 million in Q1 2024, primarily due to increased clinical trial costs and personnel expenses [8] - General and Administrative (G&A) expenses for Q1 2025 were $13.4 million, compared to $11.3 million in Q1 2024, driven by personnel-related expenses [9] - The net loss for Q1 2025 was $46.8 million, compared to a net loss of $26.0 million in Q1 2024 [10] Pipeline and Future Directions - Structure Therapeutics is exploring additional indications for GLP-1 receptor agonists beyond obesity, including Parkinson's disease, with preclinical data to be presented at the ADA 85 Scientific Sessions in June 2025 [5] - The company is also developing GIPR and GCGR selective agonists and antagonists, as well as evaluating ANPA-0073, a Phase 2 ready biased APJR agonist for potential muscle-sparing weight loss [5][6]

Core Insights - Eli Lilly is set to release initial results from late-stage clinical trials for its oral obesity pill, orforglipron, which could disrupt the weight loss drug market [2][3] - Analysts anticipate that orforglipron will be comparable in effectiveness and safety to Novo Nordisk's semaglutide, a leading weight loss injection [3][26] - The introduction of orforglipron could enhance patient access to obesity treatments and solidify Eli Lilly's market position as competitors rush to develop similar products [4][5] Clinical Trials and Efficacy - Eli Lilly plans to unveil data from five studies on Type 2 diabetes and two trials on obesity in 2025 [2] - The expected weight loss for patients using orforglipron is around 13% to 15%, which is similar to the average weight loss seen with Wegovy [28] - In a phase two trial, patients taking 36 milligrams of orforglipron lost an average of 13.5% of their body weight after 36 weeks, compared to 2.3% for the placebo group [29] Market Potential - The GLP-1 market is projected to exceed $150 billion annually by the early 2030s, with oral GLP-1s potentially capturing $50 billion of that market [6] - Eli Lilly's market value reached approximately $814 billion, with over $45 billion in revenue in 2024, largely driven by diabetes and obesity products [11] - The pill could facilitate entry into markets lacking the infrastructure for cold supply chains required for injections [14] Accessibility and Pricing - Orforglipron may be priced lower than existing injections, with expectations of a 10% to 15% discount compared to Zepbound, potentially making it 30% to 35% cheaper than Wegovy [23] - Despite the potential for lower pricing, insurance coverage for obesity medications remains uncertain, with many plans still hesitant to cover these treatments [24][22] - The pill's ease of use could attract patients who prefer oral medications over injections, especially those who are needle-averse [12][19] Competitive Landscape - Eli Lilly is approximately three years ahead of competitors like Pfizer and AstraZeneca in developing oral GLP-1 medications [5] - Positive trial results for orforglipron could validate the oral administration of GLP-1s, benefiting other companies in the space [39] - Conversely, any safety concerns or disappointing data from Eli Lilly's trials could negatively impact the perception of other non-peptide oral GLP-1s [40]

TABLE OF CONTENTS As filed with the Securities and Exchange Commission on June 3, 2024. Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Structure Therapeutics Inc. (Exact name of registrant as specified in its charter) 2834 98-1480821 (I.R.S. Employer Identification Number) (State or other jurisdiction of incorporation or organization) Classification Code Number) 601 Gateway Blvd., Suite 900 South ...

TABLE OF CONTENTS As filed with the Securities and Exchange Commission on November 17, 2023 Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 98-1480821 (I.R.S. Employer Identification Number) 601 Gateway Blvd., Suite 900 South San Francisco, CA 94080 (628) 229-9277 (Address, including zip code, and telephone number, including area code, of registrant's principal executive offices) Raymond Stevens, Ph.D. Chief Executive Officer Structure Therapeutics Inc. 601 Gate ...

As filed with the Securities and Exchange Commission on January 30, 2023. Registration No. 333-269200 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 AMENDMENT NO. 1 TO FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Structure Therapeutics Inc. (Exact name of registrant as specified in its charter) TABLE OF CONTENTS Cayman Islands 2834 98-1480821 (State or other jurisdiction of incorporation or organization) (Primary Standard Industrial Classification Code Number) 61 ...